Genetic Control by a Metabolite Binding mRNA

Nahvi, Ali; Sudarsan, Narasimhan; Ebert, Margaret S.; Zou, Xiang; Brown, Kenneth L.; Breaker, Ronald R.

doi:10.1016/s1074-5521(02)00224-7

Cited by 707 publications

(596 citation statements)

References 31 publications

Supporting

Mentioning

565

Contrasting

Unclassified

Order By: Relevance

“…This observation, coupled with their widespread phylogenetic distribution, argues that riboswitches have been evolutionarily maintained for several billion years, although considerably more research is required to fully establish these claims. To date, biochemical evidence for riboswitch function has been obtained for RNAs that respond to adenosylcobalamin [14,15], thiamine pyrophosphate (TPP) [16], flavin mononucleotide (FMN) [17,18], guanine [19], adenine [20], a precursor for queuine [21], lysine [22], glycine [23], glucosamine-6-phosphate (GlcN6P) [4], and S-adenosylmethionine (SAM) [24-26; reviewed in 27,12]. Given their ability to function as sensitive sentinels for intracellular metabolites in a protein-independent manner, these RNAs are likely to require exquisite structural sophistication.…”

Section: Riboswitches: Remnants Of An Ancient Mode Of Genetic Regulatmentioning

confidence: 99%

Structural features of metabolite-sensing riboswitches

Wakeman

Winkler

Dann

2007

Trends in Biochemical Sciences

View full text Add to dashboard Cite

Riboswitches, metabolite-sensing RNA elements found in untranslated regions of the transcripts they regulate, possess extensive tertiary structure to couple metabolite binding to genetic control. Herein, we discuss recently published structures from four riboswitch classes and compare these natural RNA structures to those of in vitro selected RNA aptamers, which bind similar ligands to those of the riboswitches. Additionally, we examine the glmS riboswitch, the first example of a ribozyme-based riboswitch. This RNA provides the latest twist in the riboswitch field and portends exciting advances in the coming years. Our knowledge of the mechanisms of genetic regulation by riboswitches has increased mightily in recent years and will continue to grow as new riboswitch classes and ligands are discovered and structurally characterized. KeywordsRNA structure; riboswitch; ribozyme; transcription attenuation; noncoding RNAs; posttranscriptional regulation; crystallography; NMR Riboswitches: Remnants of an ancient mode of genetic regulation?The "central dogma" states that information is stored as DNA, transcribed into RNA, and translated into proteins, which are traditionally thought to satisfy most cellular structural and catalytic requirements. Genetic control of these steps is believed to occur primarily through the action of regulatory proteins; however, the importance of noncoding RNAs in these processes has become increasingly appreciated in recent years [1]. In eubacterial organisms, regulatory RNAs can elicit control of gene expression through regulation of transcription attenuation, translation initiation [reviewed in 2,3], or mRNA stability [4]. These eubacterial regulatory RNAs function via diverse intermolecular (trans) or intramolecular (cis) mechanisms to regulate the target mRNA. Trans-acting regulatory RNAs interact with target mRNAs to control translation, mRNA stability, or transcription termination [reviewed in 5,6, 7], whereas others regulate gene expression through specific sequestration of RNA-binding proteins [8]. Cis-acting RNAs, which are the focus of this review, are located within untranslated regions (UTRs) of the mRNA transcript that they regulate. Genetic control by the latter RNA elements can be accomplished either through the sole action of the RNA molecule or in conjunction with recruited protein factors.A classic example of a cis-acting regulatory RNA is the transcription attenuation control of tryptophan biosynthesis genes in certain Gram-negative bacteria [9]. For this mechanism, the kinetics of translation of a short leader peptide dictates the conformational state of the overall 5′-UTR. Under tryptophan-depleted conditions the translating ribosome stalls at tryptophan codons within the leader peptide thereby allowing for formation of an antiterminator helix and [24-26; reviewed in 27,12]. Given their ability to function as sensitive sentinels for intracellular metabolites in a protein-independent manner, these RNAs are likely to require exquisite structural sophistication....

show abstract

Section: Riboswitches: Remnants Of An Ancient Mode Of Genetic Regulatmentioning

confidence: 99%

Structural features of metabolite-sensing riboswitches

Wakeman

Winkler

Dann

2007

Trends in Biochemical Sciences

View full text Add to dashboard Cite

show abstract

“…85,86 They correspond to non-coding RNA structure elements located in the leader sequence of mRNA strands, which selectively bind certain metabolites to regulate the synthesis of downstream products relevant to this metabolite. [2][3][4]11,87 This regulatory response is achieved by the coordination between the embedded metabolite-binding aptamer domain and the expression platform which switches between alternative structures upon sensing a change in the aptamer domain when a metabolite binds. 3,4,11 The riboswitch can generally assume two mutually-exclusive structures -one metabolite-bound, and one metaboliteunbound.…”

Section: Regulation Of Gene Expression Via a Riboswitchmentioning

confidence: 99%

“…Several studies have discovered RNA molecules with multiple structures which each plays a distinct functional role at different times of the molecule's life. One early example of sequences with more than one functional RNA structure is so-called riboswitch [2][3][4] which consists of two distinct, mutually exclusive RNA structures each with a distinct functional role. We thus need to start looking beyond the one-sequence-onestructure dogma to appreciate that one RNA sequence can have more than one functional structure throughout its cellular life and to understand the mechanisms underlying their regulation.…”

Section: Introductionmentioning

confidence: 99%

Four RNA families with functional transient structures

Zhu

Meyer

2015

RNA Biology

View full text Add to dashboard Cite

P rotein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since RFAM annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing RFAM families or introduce a new RNA family to RFAM. For each of the four RNA families, we compile a multiplesequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5 0 flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5 0 UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All transient and dominant structures are mapped to our new alignments introduced here.

show abstract

“…In the case of riboswitches [77,78], expression of downstream gene(s) is modulated by conformational changes induced by the interaction of a specific cellular component (e.g., metabolite, metal ion, etc.) with the 3D structure of the sensing domain, which cannot be predicted or explained according to the simple rules of base-pairing recognition [79,80]. These examples clearly highlight the need for technologies capable of providing not only the higher-order structure of non-coding elements, but also unambiguous information about the identity of cognate ligands, the nature of their interactions, and the effects of binding on structure and dynamics.…”

Section: Confronting New Challenges In the Post-genomics Eramentioning

confidence: 99%

A eole for the MS analysis of nucleic acids in the post-genomics age

Fabris

2010

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

The advances of mass spectrometry in the analysis of nucleic acids have tracked very closely the exciting developments of instrumentation and ancillary technologies, which have taken place over the years. However, their diffusion in the broader life sciences community has been and will be linked to the ever evolving focus of biomedical research and its changing demands. Before the completion of the Human Genome Project, great emphasis was placed on sequencing technologies that could help accomplish this project of exceptional scale. After the publication of the human genome, the emphasis switched toward techniques dedicated to the exploration of sequences not coding for actual protein products, which amount to the vast majority of transcribed elements. The broad range of capabilities offered by mass spectrometry is rapidly advancing this platform to the forefront of the technologies employed for the structure-function investigation of these noncoding elements. Increasing focus on the characterization of functional assemblies and their specific interactions has prompted a re-evaluation of what has been traditionally construed as nucleic acid analysis by mass spectrometry. Inspired by the accelerating expansion of the broader field of nucleic acid research, new applications to fundamental biological studies and drug discovery will help redefine the evolving role of MS-analysis of nucleic acids in the post-genomics age. (J Am Soc Mass Spectrom 2010, 21, 1-13)

show abstract

Genetic Control by a Metabolite Binding mRNA

Cited by 707 publications

References 31 publications

Structural features of metabolite-sensing riboswitches

Structural features of metabolite-sensing riboswitches

Four RNA families with functional transient structures

A eole for the MS analysis of nucleic acids in the post-genomics age

Contact Info

Product

Resources

About